The characteristics of acquired cocaine dependence, tolerance or cumulative effects and the psychologic, behavioral and physiologic subsequences of repeated oral doses of cocaine given to healthy volunteer hospitalized subjects will be measured. We will see if relatively brief (5-6 day) periods of sustained intoxication are associated with an abstinence syndrome, tolerance or alterations in drug metabolism. Frequent measure before, during and after periods of cocaine administration with cocaine sensitive measures will document on what systems and at what rate tolerance develops. Measures include symptoms and mood, cardiovascular, automonic and electroencephalographic spectra. Structured interviews, close observation and rating of behavior by nurses and self-ratings of mood and symptoms will document cocaine effects when given five or more days subchronically and the consequences of stopping cocaine, particularly rebound phenomena. Attention will be given to understanding individual differences in magnitude of effect and the progression of tolerance on cumulative effects and/or dependence. Double-blind drug or placebo administration and placebo only treatment groups will be controls. Manipulation of dose, duration and frequency of dose will test and increase understanding of general principles determining drug tolerance and dependence. The data should provide the background for subsequent controlled assessment of drug-seeking behavior and relationships between craving and cocaine tolerance/dependence. The experiments also will assess the utility of cocaine toxicity as a model psychosis, posttreament mood as a model for depression, provide a paradigm for rapid assessment of the utility of pharmacologic approaches for treating cocaine abuse, allow for studies of mechanisms, and provide data useful in planning therapeutic trails and drug interactions with cocaine. In general, the studies will explore a relatively rarely used experimental paradigm in human clinical psychopharmacology. Disciplines involved include medicine, psychopharmacology, psychopysiology, biochemistry, pharmacy and clinical pharmacology. Acute and chronic toxicity from cocaine is an increasing clinical problem. These studies under controlled conditions are directly concerned with the understanding of important variables, mechanisms and management of cocaine users needing treatment.